NCT00135187

Study of Combination Therapy With VELCADE, Doxil, and Dexamethasone (VDd) in Multiple Myeloma

A Pilot Study of Combination Therapy With VELCADE, Doxil, and Dexamethasone (VDd) in Multiple Myeloma

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: University of Michigan Rogel Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Patients are being asked to take part in this research study because they have multiple myeloma which has relapsed after (come back), or is refractory to (unaffected by), initial therapy. For patients who have relapsed or are refractory to therapy, there is no agreed upon standard treatment. Treatment options include chemotherapy and, for some patients, bone marrow transplants. None of the available treatments are curative and investigators are continually looking for more effective treatments. This study involves treatment with a new combination of standard drugs: VELCADE, Doxil, and Dexamethasone. Preliminary results from a study using a combination of VELCADE with Doxil showed high response rates (disease reduction). Two other studies showed that an addition of Dexamethasone to VELCADE in patients not responding to VELCADE alone improved response rate. The proposed combination of all three drugs may improve efficacy and response. VELCADE is approved by the Food and Drug Administration (FDA) for use in multiple myeloma. Doxil is not approved for use in multiple myeloma but is an approved drug for use in patients with some other cancers. Several published clinical trials provide evidence that Doxil is an active agent in multiple myeloma and it is used in treatment combinations for multiple myeloma in general practice. Dexamethasone is approved for use in multiple myeloma. The combination of all three drugs is experimental (not FDA approved). The goals of this study are to determine if this new combination therapy with VELCADE, Doxil and Dexamethasone is an effective treatment, and also to determine the side effects that occur when this combination treatment is given.

Detailed description

Multiple myeloma remains a non-curable disease. Combination therapies such as VAD have been effective, with partial response rates in \~40-60% range and tolerable toxicity. A recent study showed that substituting Doxil for Doxorubicin in a regimen similar to VAD (DVd) resulted in an improved toxicity profile and similar efficacy. The most active agents in VAD (and presumably in DVd) are Doxorubicin (or Doxil) and Dexamethasone, while Vincristine adds little, if at all to the efficacy of these regimen(s). One of the new active agents in multiple myeloma is VELCADE (bortezomib, formerly known as VELCADE). This molecule has a novel mechanism of action by specifically inhibiting the proteasome. A recently reported Phase II trial showed that VELCADE as a single agent induced at least minimal responses (i.e. \> 25% reduction in monoclonal protein) in 35% of patients and at least a stabilization of the disease in 59% of patients with relapsed/refractory multiple myeloma using strict SWOG criteria. An additional 18% responded when Dexamethasone was added to VELCADE. Pre-clinical observations showed that the addition of VELCADE to other chemotherapeutic agents, such as doxorubicin, enhances cytotoxicity of multiple myeloma cells. Preliminary results from Phase I study of combination of VELCADE with Doxil showed 60% response rate (i.e. \> partial response) with acceptable toxicity. In this study we propose to combine three active agents, i.e. Doxil, Dexamethasone (two most active agents from DVd), and VELCADE. The ultimate goal is to show that this combination of drugs is more efficacious than VAD or VELCADE with either Dexamethasone or Doxil and without additional toxicity.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	VELCADE	VELCADE will be used biweekly at 1.3 mg/m2 during week 1 and 2 on (days 1, 4, 8, and 11) followed by a 1-week break.
DRUG	Doxil	Doxil will be administered at 30 mg/m2 IV on day 4
DRUG	Dexamethasone	Dexamethasone at 40 mg during the first cycle and 20 mg during cycles 2-6 po or IV daily on days of VELCADE and day after VELCADE (i.e. days 1, 2, 4, 5, 8, 9, 11, 12). The patient will be treated for six 3-week cycles followed by three 5-week maintenance cycles.

Timeline

• Start date: 2004-07-01
• Primary completion: 2006-08-01
• Completion: 2007-12-01
• First posted: 2005-08-25
• Last updated: 2012-02-07

Locations

1 site across 1 country: United States